Aggregation of ￥á-Synuclein Induced by Oxidized Catecholamines as a Potential Mechanism of Lewy Body

摘要

Lewy bodies (LBs) are neuronal inclusions that are closely related to Parkinson`s disease (PD). The filamentous component of LB from patients with PD contains biochemically altered メ-synuclein. We have investigated the effect of the oxidized products of catecholamines on the modification of メ-synuclein. When メ-synuclein was incubated with the oxidized 3,4-dihydroxyphenylalanine (L-DOPA) or dopamine, the protein was induced to be aggregated. The oxidized catecholamine-mediated メ-synuclein aggregation was enhanced by copper ion. Radical scavengers, azide and N-acetyl cysteine significantly prevented the oxidized catecholamine-mediated メ-synuclein aggregation. The results suggest that free radical may play a role in メ-synuclein aggregation. Exposure of メ-synuclein to the oxidized products of catecholamines led to the formation of dityrosine. Antioxidant dipeptides carnosine, homocarnosine and anserine significantly protected メ-synuclein from the aggregation induced by the oxidized products of catecholamines.